The overall objective of these studies is to evaluate the role of lipid peroxidation in the pathogenesis of experimental atherosclerosis. The specific aims are to produce advanced forms of the disease in rabbits, to see if dietary antioxidants BHA and BHT or vitamin E affects the development of the arterial lesions, and to seek direct evidence of the possible pathogenic role of lipid peroxidation in atherogenesis. We have developed a semisynthetic, low-cholesterol atherogenic diet for rabbits that is highly palatable and results in normal weight gain, modest elevation of plasma LDL, and development of proliferative fatty streaks after 6 months, in the absence of circulating foam-cells and lipidosis of the RE system and liver. The basal diet will be fed with and without dietary antioxidants beginning at weaning, when arteries undergo extensive growth and remodeling, and continuing for at least 30 months. Animals from each group will be killed at 3,6,12, or 18 months to evaluate parameters sequentially. Analyses will include light and electron microscopy, measurement of plasma and hepatic lipids, spectrophotometric analysis of arterial tissue for diene conjugates and fluorescent pigments (ceroid, lipofuscin), and estimation of the lipid peroxidation potential of arteries by the TBA procedure. We believe that previous studies concerned with similar questions were inconclusive because of the inappropriateness of the experimental models used.